Ge Yucheng, Liu Yukun, Zhan Ruichao, Zhao Zhenqiang, Li Jun, Wang Wenying, Tian Ye
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Hum Mutat. 2023 Sep 14;2023:4875680. doi: 10.1155/2023/4875680. eCollection 2023.
Primary hyperoxaluria (PH) is a rare monogenic disorder characterized by recurrent kidney stones, nephrocalcinosis, and renal impairment. To study the genotype and phenotype characteristics, we evaluated the clinical data of 42 Chinese pediatric PH patients who were diagnosed from May 2016 to April 2022. We found that patients with the PH3 type showed an earlier age of onset than those with the PH1 and PH2 types (1 versus 5 and 8 years, respectively, < 0.001). Urine citrate was significantly lower in PH1 and PH2 patients than that in PH3 patients (91.81 and 85.56 versus 163.9 g/mg, respectively, = 0.044). Spot urine oxalate levels were slightly higher in PH1 than that in PH2 and PH3 patients (457.9 versus 182.38 and 309.14 g/mg, respectively, = 0.189). A significant negative correlation between the urine calcium/creatinine ratio and the oxalate/creatinine ratio was observed in the entire PH cohort ( = -0.360, = 0.04) and the PH3 cohort ( = -0.674, = 0.003). PH-causative genes showed hotspot mutations or regions, including c.815_816insGA and c.33dup in , 864_865del in , and exon 6 skipping and c.769T>G in . In the PH1 cohort, the estimated glomerular filtration rate (eGFR) was lowest in patients with heterozygous c.33dup. In the PH3 cohort, patients with heterozygous exon 6 skipping presented the lowest eGFR and a significant decrease in the renal survival advantage. In summary, PH1 patients exhibit much more severe phenotypes than those with other types. Hotspot mutations or regions exist in patients with all types of PH and show differences among ethnicities. Genotype-phenotype correlations are observed in PH1 and PH3.
原发性高草酸尿症（PH）是一种罕见的单基因疾病，其特征为复发性肾结石、肾钙质沉着症和肾功能损害。为研究基因型和表型特征，我们评估了2016年5月至2022年4月期间确诊的42例中国儿科PH患者的临床资料。我们发现，PH3型患者的发病年龄比PH1型和PH2型患者更早（分别为1岁、5岁和8岁，<0.001）。PH1和PH2患者的尿枸橼酸盐显著低于PH3患者（分别为91.81和85.56对比163.9 g/mg，=0.044）。PH1患者的随机尿草酸水平略高于PH2和PH3患者（分别为457.9对比182.38和309.14 g/mg，=0.189）。在整个PH队列（= -0.360，=0.04）和PH3队列（= -0.674，=0.003）中，观察到尿钙/肌酐比值与草酸/肌酐比值之间存在显著负相关。PH致病基因显示热点突变或区域，包括 中的c.815_816insGA和c.33dup、 中的864_865del以及 中的外显子6跳跃和c.769T>G。在PH1队列中，杂合子c.33dup患者的估计肾小球滤过率（eGFR）最低。在PH3队列中，杂合子外显子6跳跃的患者eGFR最低，且肾脏生存优势显著降低。总之，PH1患者的表型比其他类型患者严重得多。所有类型的PH患者均存在热点突变或区域，且在不同种族之间存在差异。在PH1和PH3中观察到基因型-表型相关性。
